The present invention is directed toward the treatment of gastrointestinal disease through a transdermally administered antisecretory agent. Antisecretory agents shown to be useful for transdermal administration are substituted 2-pyridylmethylthio- and sulfinyl-benzimidazoles and omeprazole.
One means for preventing or treating gastrointestinal diseases, specifically gastric and duodenal ulcers, is by the inhibition of gastric acid secretion. In situations where the integrity of the gastric mucosal barrier is compromised, gastric acid secretion can result in erosion of the epithelial cells with consequent inflammation and ulceration. Prevention and healing of such untoward gastric acid-induced effects can be achieved by the administration of a pharmacological agent which effectively inhibits gastric acid secretion.
Various effective agents are known such as substituted 2-pyridylmethylthio- and sulfinyl-benzimidazoles which are described in U.S. Pat. No. 4,575,554 and are herein incorporated by reference. Omeprazole is another compound known to be effective for the inhibition of gastric acid secretion which is described in U.S. Pat. No. 4,255,431 herein incorporated by reference.
Another important aspect to the prevention or treatment of gastrointestinal disease is the continuous, rather than intermittant, inhibition of gastric acid. It is therefore desirable to administer the drugs in a slow continuous fashion over a long period of time such that excess gastric acid secretion is minimized to prevent gastrointestinal disease. Another important consideration is ease of administration and comfort.
U.S. Pat. No. 4,575,554 discloses that a continuous inhibition of acid can be achieved by administering a single dose of these compounds subcutaneously. Until this time, subcutaneous administration of this class of compounds was the only choice when a long duration of action (several days or weeks) is desired with a single dose. Unfortunately, subcutaneous injection are not comfortable and sometimes can cause irritation to the surrounding tissue. Also, in the event of toxicity problems removal is difficult.
Transdermal administration of drugs such as by patches, gels, pastes, or other known vehicles is not only convenient but for the most part painless, simple to apply and easy to remove during adverse reactions. Unfortunately, many drugs can not be applied in this manner because they do not cross the skin readily enough to give the desired efficacy. Unexpectedly it has been discovered that the class of gastric anti-secretory drugs, substituted 2-pyridylmethylthio- and sulfinyl-benzimidazoles and omeprazoles, can be administered transdermally and still effectively inhibit the enzyme responsible for gastric acid secretion.